J Am Soc Nephrol

A randomized study comparing methylprednisolone plus chlorambucil versus methylprednisolone plus cyclophosphamide in idiopathic membranous nephropathy.

Year 1998
Ponticelli C. Altieri P. Scolari F. Passerini P. Roccatello D. Cesana B. Melis P. Valzorio B. Sasdelli M. Pasquali S. Pozzi C. Piccoli G. Lupo A. Segagni S. Antonucci F. Dugo M. Minari M. Scalia A. Pedrini L. Pisano G. Grassi C. Farina M. Bellazzi R.
Divisione di Nefrologia e Dialisi, Ospedale Maggiore Policlinico IRCCS, Milano, Italy.
To assess whether chlorambucil or cyclophosphamide may have a better therapeutic index in patients with idiopathic membranous nephropathy, we compared two regimens based on a 6-mo treatment, alternating every other month methylprednisolone with chlorambucil or methylprednisolone with cyclophosphamide. Patients with biopsy-proven membranous nephropathy and with a nephrotic syndrome were randomized to be given methylprednisolone (1 g intravenously for 3 consecutive days followed by oral methylprednisolone, 0.4 mg/kg per d for 27 d) alternated every other month either with chlorambucil (0.2 mg/kg per d for 30 d) or cyclophosphamide (2.5 mg/kg per d for 30 d). The whole treatment lasted 6 mo; 3 mo with corticosteroids and 3 mo with one cytotoxic drug. Among 87 patients followed for at least 1 yr, 36 of 44 (82%; 95% confidence interval [CI], 67.3 to 91.8%) assigned to methylprednisolone and chlorambucil entered complete or partial remission of the nephrotic syndrome, versus 40 of 43 (93%; 95% CI, 80.9 to 98.5%) assigned to methylprednisolone and cyclophosphamide (P = 0.116). Of patients who attained remission of the nephrotic syndrome, 11 of 36 in the chlorambucil group (30.5%) and 10 of 40 in the cyclophosphamide group (25%) had a relapse of the nephrotic syndrome between 6 and 30 mo. The reciprocal of plasma creatinine improved in the cohort groups followed for 1 yr for both treatment groups (P < 0.01) and remained unchanged when compared with basal values in the cohort groups followed for 2 and 3 yr. Six patients in the chlorambucil group and two in the cyclophosphamide group did not complete the treatment because of side effects. Four patients in the chlorambucil group but none in the cyclophosphamide group suffered from herpes zoster. One patient per group developed cancer. It is concluded that in nephrotic patients with idiopathic membranous nephropathy both treatments may be effective in favoring remission and in preserving renal function for at least 3 yr.

New criteria for management of catheter infections in peritoneal dialysis patients using ultrasonography.

Year 1998
Vychytil A. Lorenz M. Schneider B. Horl WH. Haag-Weber M.
Department of Medicine III, University Hospital of Vienna, Austria.
Catheter-related infection is one of the most important causes of technical dropout in peritoneal dialysis patients. Both the type of cultured organism and the extent of inflammation are well known prognostic factors for the outcome of these infections. From December 1994 to November 1996, 96 catheter-related infections without simultaneous peritonitis occurred in 49 of 86 peritoneal dialysis patients treated in this study. During the observation period, only single-cuff catheters were used. Staphylococcus aureus was the most common organism cultured (51%). Involvement of the tunnel was diagnosed by sonography in 57.1% of all Staphylococcus aureus cases, but only in 26.1% of Staphylococcus epidermidis-related exit-site infections. Ten of the 96 catheter-related infections (10.4%) resulted in catheter loss. Catheter removal was necessary only in cases of deep tunnel infection caused by Staphylococcus aureus. The number of gram-negative catheter infections was too small to allow conclusive analysis. Although sonography of the catheter tunnel is now well established in the early diagnosis of tunnel infections, no clear guidelines exist for management of these infections. In this study, patients with deep tunnel infection who did not require catheter removal showed a significant decline of the hypoechogenic area around the cuff (from 7.02 +/- 0.70 to 3.75 +/- 1.04 mm, P < 0.002) 2 wk after initiation of therapy. No significant decline was observed in patients who later lost their catheters. On the basis of these data, it is concluded that in cases of exit-site and superficial tunnel infection, conservative treatment should be performed. In cases of deep tunnel infection without peritonitis caused by Staphylococcus aureus, antibiotic treatment should be started and sonographic examination should be performed every second week. If the hypoechogenic area around the cuff decreases (> 30%), conservative treatment should be prolonged. In cases without sonographic improvement (< 30%) 2 wk after therapy, catheter removal is recommended.

New strategies to prevent Staphylococcus aureus infections in peritoneal dialysis patients.

Year 1998
Vychytil A. Lorenz M. Schneider B. Horl WH. Haag-Weber M.
Department of Medicine III, University Hospital of Vienna, Austria.
The importance of Staphylococcus aureus as etiological agent for catheter-related infections and peritonitis in peritoneal dialysis patients is well established. To evaluate groups at risk of developing Staphylococcus aureus infections, nasal and exit-site cultures were performed in 76 peritoneal dialysis patients monthly over a period of 3 yr. The risk of Staphylococcus aureus catheter infection was significantly higher in diabetic (group 1) and immunosuppressed (group 2) patients compared with nondiabetic and nonimmunosuppressed (group 3) patients. In diabetic patients, Staphylococcus aureus-positive nasal cultures were more frequent than positive cultures taken from the bland exit-site (73.3% versus 60.0%). On the other hand, both positive and negative exit-site cultures had a better prognostic value for Staphylococcus aureus catheter infection compared with nasal cultures. In immunosuppressed patients, both nasal and exit-site carriages were associated with a very high risk of Staphylococcus aureus catheter infection, but nasal swabs were far more often positive than swabs from the bland exit-site (72.7% versus 25.0%). However, the risk of infection was also high for non-nasal and non-exit-site carriers in this group. In nondiabetic and nonimmunosuppressed patients, the risk of Staphylococcus aureus catheter infection was increased only if two or more positive nasal cultures were detected. It is concluded that in diabetic patients, antibiotic prophylaxis should be performed in all Staphylococcus aureus exit-site carriers. All immunosuppressed patients should be treated prophylactically. In contrast, in nondiabetic and nonimmunosuppressed patients, prophylactic treatment should be considered only in nasal carriers with two or more positive cultures. The overall low peritonitis rate does not influence this prevention strategy.

Fibrosing cholestatic hepatitis in hepatitis C virus-infected renal transplant recipients.

Year 1998
Munoz De Bustillo E. Ibarrola C. Colina F. Castellano G. Fuertes A. Andres A. Aguado JM. Rodicio JL. Morales JM.
Department of Nephrology, Hospital 12 de Octubre, Madrid, Spain.
Severe hepatitis C virus (HCV)-related fibrosing cholestatic hepatitis leading to early liver failure has been reported only exceptionally. Of 259 HCV-infected renal transplant (RT) patients in one hospital unit, four (1.5%) are described, representing the first series of this particular post-RT disease. Patient mean age was 55.7 yr. Three were men. All had pretransplant, hepatitis B surface antigen-negative and were anti-HCV antibodies positive. Three of them showed pretransplant mild liver enzyme abnormalities, and all received kidneys from HCV-negative donors. All were on steroids, cyclosporine, and azathioprine (AZA). The clinical pattern appeared early after RT (mean, 11.5 mo). In three patients, hyperbilirubinemia (6.5 to 20 mg/dl) and high alkaline phosphatase levels (428 to 859 IU/L) were observed. Also, in all subjects, high gamma glutamyl transpeptidase levels (639 to 4270 IU/L), mild aspartate aminotransferase and alanine aminotransferase abnormalities, and serum HCV RNA were observed. Liver biopsy revealed diffuse fibrosis, leukocyte infiltrates, and different degrees of cholestasis, with typical signs of HCV hepatitis in only one patient. Two patients developed subfulminant liver failure and died 2 and 3 mo after biopsy, respectively. One patient also suffered hepatic failure, receiving a liver transplant. The fourth is alive on dialysis awaiting a combined kidney and liver transplant. It is concluded that fibrosing cholestatic hepatitis is a new, early, and severe complication after RT in HCV(+) patients, which appears in patients with ongoing HCV infection under AZA therapy, despite a nonaggressive immunosuppressive protocol. Both HCV and AZA could play a concurrent role in the pathogenesis of this severe complication after RT.